Project Summary Adolescents appear to be particularly vulnerable to begin using tobacco and other nicotine (NIC)-containing products. NIC exposure during adolescence may have long-lasting effects on adult behavior, promoting continued use of NIC-containing products in adulthood. This is especially important in the context of a potential tobacco regulatory policy limiting NIC content in tobacco products. Will adolescent NIC use impact how adults will respond to low NIC products? Will adolescent use of very low doses of NIC minimize the impact of adolescent exposure to NIC on adult NIC use? Alternatively, might it promote the use of NIC products in adulthood? The goal of the experiments presented in this proposal is to determine, using a rodent model of NIC self-administration (SA), the impact of NIC use during adolescence on the use of very low NIC content (VLNC) cigarettes in adulthood. Embedded in this is whether or not adolescent use of NIC-containing products serves as a gateway to smoking and whether NIC reduction could minimize this risk. The current R21 application is designed around two specific aims. Aim 1 tests the hypothesis that NIC SA during adolescence (either low or standard dose of NIC) increases adult NIC SA, especially at low doses of NIC. To address this question, adolescent male and female rats will be allowed to self-administer a low or a more standard dose of NIC starting in early adolescence and then the NIC dose will be changed when they are adults. The key measure will be amount of NIC SA in adulthood, and how that is altered by different doses of adolescent NIC SA. Aim 2 tests the hypothesis that NIC SA during adolescence (either low or standard dose) increases the motivation to seek NIC in adulthood. This hypothesis will be tested at the end of Aim 1 by examining responding for NIC on a progressive ratio schedule of reinforcement in adult rats that self-administered NIC throughout adolescence and into adulthood. An important component of these experiments is that NIC will be self-administered along with a mildly reinforcing environmental stimulus, to incorporate the reinforcement enhancement actions of NIC, which are an essential behavioral component driving NIC use. These experiments will help understand the potential long-term consequences of adolescent NIC exposure on continued use of NIC-containing products and will have important implications in the context of potential NIC reduction tobacco regulatory policy. This proposal fits with the RFA Research Objective focused on addiction and the characteristics of tobacco products that may impact addiction as well as understanding the behaviors related to tobacco product use. Here we focus on the adolescent exposure to NIC-containing products and on other salient stimuli coupled with NIC delivery in supporting NIC SA or motivation to obtain NIC.